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dc.contributor.authorFirestein, Ron
dc.contributor.authorGupta, Piyush
dc.contributor.authorRepich, Kara
dc.contributor.authorSilver, Serena J.
dc.contributor.authorBoehm, Jesse S.
dc.contributor.authorKim, So Young
dc.contributor.authorDunn, Ian Frederick
dc.contributor.authorWardwell, Leslie
dc.contributor.authorSchinzel, Anna
dc.contributor.authorWittner, Ben
dc.contributor.authorRoot, David E.
dc.contributor.authorRamaswamy, Sridhar
dc.contributor.authorLander, Eric Steven
dc.contributor.authorHahn, William C.
dc.date.accessioned2013-01-18T19:48:46Z
dc.date.issued2010
dc.identifier.citationKim, So Young, Ian F. Dunn, Ron Firestein, Piyush Gupta, Leslie Wardwell, Kara Repich, Anna C. Schinzel, et al. 2010. CK1\(\varepsilon\) is required for breast cancers dependent on \(\beta\)-catenin activity. PLoS ONE 5(2): e8979.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10198945
dc.description.abstractBackground: Aberrant \(\beta\)-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate \(\beta\)-catenin activity for therapeutic purposes have proven elusive to date. Methodology: To uncover genetic dependencies in breast cancer cells that harbor active \(\beta\)-catenin signaling, we performed RNAi-based loss-of-function screens in breast cancer cell lines in which we had characterized \(\beta\)-catenin activity. Here we identify CSNK1E, the gene encoding casein kinase 1 epsilon (CK1\(\varepsilon\)) as required specifically for the proliferation of breast cancer cells with activated \(\beta\)-catenin and confirm its role as a positive regulator of \(\beta\)-catenin-driven transcription. Furthermore, we demonstrate that breast cancer cells that harbor activated \(\beta\)-catenin activity exhibit enhanced sensitivity to pharmacological blockade of Wnt/\(\beta\)-catenin signaling. We also find that expression of CK1\(\varepsilon\) is able to promote oncogenic transformation of human cells in a \(\beta\)-catenin-dependent manner. Conclusions/Significance: These studies identify CK1\(\varepsilon\) as a critical contributor to activated \(\beta\)-catenin signaling in cancer and suggest it may provide a potential therapeutic target for cancers that harbor active \(\beta\)-catenin. More generally, these observations delineate an approach that can be used to identify druggable synthetic lethal interactions with signaling pathways that are frequently activated in cancer but are difficult to target with the currently available small molecule inhibitors.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi://10.1371/journal.pone.0008979en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813871/pdf/en_US
dash.licenseLAA
dc.subjectcancer geneticsen_US
dc.subjectfunctional genomicsen_US
dc.subjectoncologyen_US
dc.subjectbreast canceren_US
dc.subjectgeneticsen_US
dc.subjectgenomicsen_US
dc.titleCK1\(\varepsilon\) is Required for Breast Cancers Dependent on \(\beta\)-Catenin Activityen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorLander, Eric Steven
dc.date.available2013-01-18T19:48:46Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0008979*
dash.authorsorderedfalse
dash.contributor.affiliatedSchinzel, Anna
dash.contributor.affiliatedWittner, Ben
dash.contributor.affiliatedRamaswamy, Sridhar
dash.contributor.affiliatedHahn, William
dash.contributor.affiliatedLander, Eric
dash.contributor.affiliatedDunn, Ian


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